• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.65-71
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• 2013

The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed non-selective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body $Mg^{2+}$ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-${\kappa}B$ ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of $Mg^{2+}$. Knock-down of TRPM7 by siTRPM7 reduced intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increases by 0 mM $[Mg^{2+}]_e$ in HEK293 cells and inhibited the generation of RANKL-induced $Ca^{2+}$ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced $[Ca^{2+}]_i$ oscillations that triggers the late stages of osteoclastogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.1-9
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• 2017

Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.315-320
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• 2013

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

• Preventive Nutrition and Food Science
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• v.19 no.2
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• pp.82-88
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• 2014

Yam (Dioscorea batatas Decne.) has long been used as a health food and oriental folk medicine because of its nutritional fortification, tonic, anti-diarrheal, anti-inflammatory, antitussive, and expectorant effects. Reactive oxygen species (ROS), which are known to be implicated in a range of diseases, may be important progenitors of carcinogenesis. The aim of this study was to investigate the modulatory effect of yam on antioxidant status and inflammatory conditions during azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We measured the formation of aberrant crypt foci (ACF), hemolysate antioxidant enzyme activities, colonic mucosal antioxidant enzyme gene expression, and colonic mucosal inflammatory mediator gene expression. The feeding of yam prior to carcinogenesis significantly inhibited AOM-induced colonic ACF formation. In yam-administered rats, erythrocyte levels of glutathione, glutathione peroxidase (GPx), and catalase were increased and colonic mucosal gene expression of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and GPx were up-regulated compared to the AOM group. Colonic mucosal gene expression of inflammatory mediators (i.e., nuclear factor kappaB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, and interleukin-1beta) was suppressed by the yam-supplemented diet. These results suggest that yam could be very useful for the prevention of colon cancer, as they enhance the antioxidant defense system and modulate inflammatory mediators.

• BMB Reports
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• v.47 no.11
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• pp.649-654
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• 2014

Neutrophils play an important role in the initiation of innate immunity against infection and injury. Although many different types of G-protein coupled receptors are functionally expressed in neutrophils, no reports have demonstrated functional expression of umami taste receptor in these cells. We observed that mouse neutrophils express the umami taste receptor T1R1/T1R3 through RNA sequencing and quantitative RT-PCR analysis. Stimulation of mouse neutrophils with L-alanine or L-serine, which are ligands for the umami taste receptor, elicited not only ERK or p38 MAPK phosphorylation but also chemotactic migration. Moreover, addition of L-alanine or L-serine markedly reduced the production of several cytokines including $TNF-{\alpha}$ induced by lipopoly-saccharide (LPS) through inhibition of $NF-{\kappa}B$ activity or STAT3 phosphorylation in neutrophils. Our findings demonstrate that neutrophils express the umami taste receptor, through which tastants stimulate neutrophils, resulting in chemotactic migration, and attenuation of LPS-induced inflammatory response.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.2 s.33
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• pp.77-88
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• 2007

Objectives : This experimental study was performed to investigate the effects of Yeouigeumhwang-san(YUGHS) on anti-inflammation and anti-Propionibacterium acnes. Methods : The cytotoxicity of YUGHS about viability of Raw 264.7 cell was tested by using a colorimetric tetrazolium assay(MTT assay). To investigate the anti-inflammatory effets of YUGHS on LPS-induced macrophage Raw 264.7 cell, we used ELISA kit and Western blots. Inhibitory effects of YUGHS on Propionibactrium acnes were investigated by using paper disk diffusion method. Results : 1. YUGHS has no cytotoxicity under 50 ${\mu}g/ml$ concentration but over 50 ${\mu}g/ml$ has a little cytotoxicity in Raw 264.7 cell. 2. Concentration of 100 ${\mu}g/ml$ YUGHS inhibited the production of NO in the Raw 264.7 cell stimulated with LPS. 3. All concentrations of YUGHS did not inhibit the production of $TNF-{\alpha}$ in the Raw 264.7 cell stimulated with LPS. 4. All concentrations of YUGHS significantly inhibited the production of $PGE_2$ in the Raw 264.7 cell stimulated with LPS. 5. YUGHS did not inhibit the expression of COX-2 but concentration of 50 ${\mu}g/ml$ YUGHS inhibited iNOS expression in the Raw 264.7 cell stimulated with LPS. 6. YUGHS has the effect of blocking $NF-{\kappa}B$ into nucleus in LPS-induced macrophage Raw 264.7 cell 7. YUGHS did not have the inhibitory effect of Propionibactrium acnes. Conclusions : These results indicate that Yeouigeumhwang-san has anti-inflammatory effets. If further study is performed, the use of Yeouigeumhwang-san will be valuable and benificial in the therapy of acnes.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.135-141
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• 2015

Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune-regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti-inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro-inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-${\alpha}$-induced degradation and phosphorylation of $I{\kappa}B$ in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis.

• BMB Reports
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• v.48 no.7
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• pp.407-412
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• 2015

The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression. [BMB Reports 2015; 48(7): 407-412]

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.443-449
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• 2001

Previously we reported that THI 52 inhibits tumor necrosis factor $(TNF)-{\alpha}$ mRNA expression in mouse peritoneal macrophages exposed to LPS plus $IFN-{\gamma}.$ In the present study, the effects of THI 52 on vascular reactivity ex vivo, and iNOS protein expression (rat lung) were investigated in LPS-treated rats. Treatment of THI 52 concentration-dependently reduced not only serum nitrite production but also the expression of iNOS protein in rat lung tissues. Thoracic aorta taken from LPS injected rat for 8 h ex vivo resulted in suppression of vasoconstrictor effects to phenylephrine (PE), which was restored by THI 52 (20 mg/kg) 30 min prior to LPS. When measured iNOS activity, treatment of THI 52 concentration-dependently reduced the enzyme activity in RAW 264.7 cells activated with LPS plus $IFN-{\gamma}.$ Likewise, iNOS activity was significantly reduced in lung tissues taken those rats that were injected THI 52 prior to LPS injection compared with LPS injection alone. These results strongly suggest that THI 52 can suppress iNOS gene expression induced by LPS, and restore the vascular contractility to PE. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where production of NO is excessed by iNOS expression.